The Prognostic Impact of t(14;20) in Multiple Myeloma - a Multicenter Retrospective Study of 26 Patients

Abstract Introduction The prognosis in multiple myeloma (MM) is based upon complex biological and clinical features. One of the strongest predictors of outcome are the intrinsic genetic abnormalities in the malignant plasma cells. t(14;20), as other chromosome 14 abnormalities, deregulates the c-musculoaponeurotic fibrosarcoma (c-MAF) oncogene. Due to the relative rarity of t(14;20) [<1.5% of newly diagnosed MM; slightly higher in monoclonal gammopathies of unknown significance- about 5%], there are no large databases which provide the natural history of this abnormality. Its meaning remains controversial due to the small sample sizes in previously published reports in contrast to t(4;14) and 17p- abnormalities which have been described independently in the literature. Methods We retrospectively analyzed the clinical features and outcomes of patients t(14;20) from 5 clinical centers in Germany, Italy and the United States. Newly diagnosed MM patients according to the International Myeloma Working Group (IMWG) criteria were enrolled. The t(14;20) was detected by double color fluorescence in situ hybridization (FISH) using bone marrow samples. Baseline characteristics at diagnosis, comorbidities, patient treatment regimens and clinical outcomes were collected using unified case report forms. Clinical responses were assessed according to the IMWG uniform response criteria. Overall survival (OS) was defined as the period between the date of initial diagnosis and the date of death or the date of the last observation. Progression-free survival (PFS) was defined as the period between the date of initial diagnosis and either the date of the first relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors of death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank and Breslow-Gehan-Wilcoxon tests. Results 26 patients were included in analysis including 11 males (42.3%). Median age at MM diagnosis was 68.5 years (range 56-71). Immunoglobulin isotype included: IgG (n=14, 53.8%), IgA (n=9, 34.6%), light chain (n=3, 11.5%). R-ISS stage at diagnosis included: stage III (n=8, 30.8%); stage II (n=9, 34.6%) and stage I (n=1, 3.8%)- the staging for remaining 8 patients is unknown. Anemia (<10g/dl) was observed in 13 (50%), impaired renal function (creatinine clearance <40 mL per minute or serum creatinine >2 mg/dl) in 3 (11.5%). In 14 (53.8%) cases osteolytic lesions were present. In 15 patients (57.7%) the t(14;20) was associated with other cytogenetic aberrations, including del17p in 2 patients (7.7%), t(4;14) in 5 patients (19.2%) and t(14;16) in 4 patients (15.4%). First line treatment for MM included mostly PIs + IMIDs in 8 patients (30.8%), PIs + IMIDs + chemotherapy in 7 patients (26.9%) or PIs alone in 3 cases (11.5%). Auto-PBSCT was performed in 8 cases (30.7%). Median PFS was 30 months (CI 95% 17.8 months; Figure 1, panel A). Median OS was not reached (Figure 1, panel B). 5-year OS from MM diagnosis was 77.5% (±10.6%). Conclusion In this study of 26 patients with t(14;20) the median PFS and 5-year OS were 30 months and not reached, respectively. Historically, the presence of a t(14;20) is considered to be a very poor prognostic factor-this was not observed in this multi-institutional retrospective analysis. In comparison to the recent studies (Ross et al, Haematologica, 2010; n=27; median survival 14.4 months), the PFS and OS of patients with t(14;20) in our analysis are better than expected. It should be highlighted that most probably in the Ross et al. study patients were not treated with novel drug therapies. Nonetheless, this controversy remains to be elucidated in the future studies. Figure 1. Figure 1. Disclosures Castillo: Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Millennium: Research Funding; Abbvie: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding. Hari:Celgene: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria. Goldberg:COTA Inc.: Employment, Equity Ownership.